Chapter 113 – Hypertensive Retinopathy
ADAM H. ROGERS
Chronic Hypertensive Retinopathy
Malignant Acute Hypertensive Retinopathy
• Retinal vascular changes occurring from chronically elevated systemic arterial hypertension.
• Narrowing and irregularity of retinal arteries.
• Arteriovenous nicking (narrowing of retinal veins at arteriovenous crossing sites).
• Blot retinal hemorrhages.
• Cotton-wool spots.
• Retinal venous obstruction.
• Retinal neovascularization.
• Retinal arterial emboli.
• Retinal, choroidal, and optic nerve changes secondary to acutely elevated systemic arterial blood pressure.
• Retinal arteriolar spasm.
• Superficial retinal hemorrhages.
• Cotton-wool spots.
• Serous retinal detachment.
• Optic disc edema.
• Choroidal ischemia.
• Retinal pigment epithelial changes.
• Optic neuropathy.
• Cortical blindness.
• Proteinuria, stroke, kidney failure, encephalopathy.
Hypertensive retinopathy represents the ophthalmic findings of end-organ damage secondary to systemic arterial hypertension. Although its name implies only retinal involvement, changes in both the choroid and the optic nerve are observed, depending on the chronicity and severity of the disease. Ocular changes in malignant hypertension can be striking, with optic neuropathy, choroidopathy, and retinopathy. Changes from essential hypertension are subtler, affecting primarily the retinal vasculature. Because hypertension is so prevalent in industrialized countries, hypertensive retinopathy is a common condition encountered by all ophthalmologists and health care professionals.
EPIDEMIOLOGY AND PATHOGENESIS
Systemic arterial hypertension is one of the most common diseases of adults in industrialized countries. Although the medical literature subdivides hypertension into multiple groups, only essential (primary) and malignant hypertension are relevant to a discussion of hypertensive retinopathy. Essential hypertension is of unknown cause and is diagnosed when the average blood pressure measures greater than 140?mmHg systolic or 90?mmHg diastolic on at least two subsequent visits. In the United States alone, it is estimated that more than 25% of all adults and 60% of persons older than 60 years are affected. Blacks have a higher prevalence of hypertension than whites, and men are affected more than women.  However, over age 50, women have a higher prevalence than men. Elevated blood pressure is rare in agrarian societies and in individuals who are physically active.
Because high blood pressure is an asymptomatic disease, most patients remain undiagnosed or inadequately treated despite the relative ease of detection. In the National Health and Nutrition Study (NHANES III) that evaluated hypertensive adults aged 18 to 74 years, 68.4% were aware of their hypertension, 53.6% were receiving treatment, and only 27.4% had their hypertension under control.  Untreated or inadequately treated hypertension carries significant cardiovascular mortality. In patients with borderline hypertension, the relative risk of cardiovascular disease and end-stage renal disease is nearly double compared with patients with “optimal” blood pressure.
The incidence of hypertensive retinal changes is variable and is often confounded by the presence of other retinal vascular disease, such as diabetes. In the Beaver Dam Eye Study, which evaluated hypertensive patients without coexisting, confounding vascular diseases, the overall incidence of hypertensive retinopathy was about 15%; specifically, 8% showed retinopathy, 13% showed arteriolar narrowing, and 2% showed arteriovenous nicking. The predictive value of diagnosing systemic hypertension from ophthalmic findings on examination was only 47–53%, demonstrating that measurement of blood pressure is a more accurate means of diagnosis. The highest frequency of hypertensive retinopathy in the study population was identified in subjects with poor blood pressure control.
Malignant hypertension is a rare syndrome consisting of rapid and severe elevation of blood pressure, with the systolic component above 200?mmHg or the diastolic blood pressure greater than 140?mmHg. Although the absolute blood pressure measurement is important, the presence of systemic findings defines malignant hypertension. These include ocular, cardiac, renal, and cerebral injury. Persistently elevated malignant hypertension can lead to a rapidly fatal course, with heart failure, myocardial infarction, stroke, or renal failure.
Nearly 1% of hypertensive patients develop malignant hypertension, and it is rare for patients to present initially with this form of elevated blood pressure. Most have a preexisting diagnosis
of either primary or secondary hypertension. Malignant hypertension rarely occurs in individuals receiving treatment for hypertension. The average age at diagnosis is 40 years, with men affected more than women. With the advent of effective antihypertensive treatment, nearly 50% of patients survive more than 5 years.
Heredity and environmental factors have been implicated in the pathogenesis of essential hypertension. In the elderly, an increase in basal smooth muscle tone occurs as a result of sympathetic overactivity with increases in the renin-angiotensin system. Other factors include salt sensitivity, low systemic calcium, and insulin resistance with hyperinsulinemia. Secondary hypertension is due to an identifiable cause, usually related to an alteration in hormone secretion or renal function. With correction of the underlying cause, this form of hypertension can be cured. The pathogenesis of malignant hypertension, similar to essential hypertension, is unknown. Research has focused on overactivity of the renin-angiotensin-aldosterone system, with high plasma renin-angiotensin levels as the cause.
Chronic Hypertensive Retinopathy
Patients with hypertensive retinopathy are usually asymptomatic. Common clinical findings include focal constriction and dilatation of the retinal arterioles, tortuosity of the retinal arterioles, an increase in the arteriolar light reflex, and loss of transparency of the intra-arterial blood column ( Fig. 113-1 ). Arteriovenous nicking is a highly specific finding and the hallmark
Figure 113-1 Mild to moderate chronic hypertensive retinopathy. Note the color change in the retinal arterioles and the early arteriovenous crossing changes.
Figure 113-2 In this 15° view, note the arteriovenous crossing changes, presence of collateral vessels, and dilated capillary bed.
of chronic hypertensive retinopathy. At the arteriovenous crossings in the retina, the vessels share a common adventitial sheath. Arteriovenous nicking is diagnosed when the crossing retinal vein becomes less apparent or even disappears on either side of the artery ( Fig. 113-2 ). The course of the vein may change to a more perpendicular direction as well. If there is impedance to flow, the segment of the vein distal to the constriction appears larger, darker, and more tortuous. Additional signs of impedance to flow are retinal hemorrhages, macular edema, and cotton-wool spots ( Fig. 113-3 ). In areas of frank obstruction, the presence of venous–venous collaterals may be long-standing. Secondary ocular complications of chronic systemic arterial hypertension include retinal vascular occlusive disease, macroaneurysm formation, and nonarteritic anterior ischemic optic neuropathy. For the differential diagnosis, see Box 113-1 .
The appearance of the ocular fundus in hypertension is related directly to the status of the retinal arteries and the rate of rise and degree of systemic blood pressure. The age of the patient may complicate interpretation of the clinical fundus changes. Although arteriolar sclerosis is a finding of long-standing hypertension, these changes, categorized as involutional sclerosis, also occur in the normal aging population. With atherosclerosis alone, mild thickening of the arteriolar wall occurs. Clinically, focal narrowing and straightening of the retinal arterioles are seen in the absence of arteriovenous crossing changes. Because the chronic effects of elevated systemic blood pressure occur along with arteriosclerotic thickening of the blood vessel walls, it can be difficult to categorize fundus changes solely on the basis of elevated blood pressure.
Malignant Hypertensive Retinopathy
Visual disturbances are common in malignant hypertension. Symptoms include headache, scotoma, diplopia, dimness in vision, and photopsia. Ocular findings in malignant arterial hypertension are divided into three distinct categories: hypertensive retinopathy, hypertensive choroidopathy, and hypertensive optic neuropathy. The cause of these clinical findings includes
Differential Diagnosis of Chronic Hypertensive Retinopathy
Retinal venous obstruction
Congenital hereditary retinal arterial tortuosity
Ocular ischemic syndrome
Figure 113-3 A 60° view of the same patient as shown in Figure 113-2 . Note the telangiectatic vessels on the optic nerve head and intraretinal hemorrhages temporal to the macula.
constriction of vascular beds from circulating catecholamines, obstruction of arterioles, and breakdown in the blood-retina barrier. Ophthalmic findings in acute malignant hypertensive retinopathy include focal arteriolar narrowing, cotton-wool spots, intraretinal transudates, macular edema, and retinal hemorrhages. Retinal hemorrhages are linear, occurring in the nerve fiber layer in the peripapillary region. Cystoid macular edema, lipid deposits, and arteriolar changes are signs of more chronic malignant hypertensive retinopathy.
Arteriolar narrowing observed on ophthalmoscopy has been challenged by Hayreh, who refers to this clinical finding as “pseudonarrowing” secondary to retinal edema creating a visual effect of narrowing of the retinal arteriole. Fluorescein angiography performed in rhesus monkeys with acute malignant hypertension has demonstrated normal retinal arteriolar caliber, casting doubt on the long-standing belief that arteriolar spasm occurs. Cotton-wool spots are fluffy, elevated, tan-white areas of retinal opacity occurring within a few disc diameters of the optic nerve, caused by occlusion of terminal retinal arterioles. Capillary nonperfusion is present on angiography ( Fig. 113-4 ). Cotton-wool spots typically resolve in 3–6 weeks and are associated with permanent nerve fiber layer loss in the vicinity of the lesion. Periarteriolar intraretinal transudates are tan-white retinal lesions occurring in the vicinity of an arteriole. The lesions measure about one quarter of the disc area but are clinically larger, as they coalesce with adjacent lesions. Intraretinal transudates occur secondary to focal areas of arteriolar leakage identified on angiography and resolve without residual retinal damage in 2–3 weeks. Macular edema and subretinal fluid are retinal findings related to hypertensive choroidal changes affecting the retinal pigment epithelium (RPE), with alterations in the blood-retina barrier.
Figure 113-4 The right eye of the same patient as shown in Figures 113-2 and 113-3 . A, A prominent cotton-wool spot in the papillomacular bundle is seen, with an adjacent intraretinal hemorrhage. B, Fluorescein angiography shows capillary nonperfusion in the area corresponding to the cotton-wool patch; note the hypofluorescence of the intraretinal hemorrhage, caused by blockage.
Clinical changes from hypertensive choroidopathy are directly related to the release of endogenous vasoconstrictor agents (e.g., angiotensin II, epinephrine, vasopressin) during systemic hypertension. Angiographically, there is delayed, patchy choroidal filling. Gitter et al. demonstrated through the use of fluorescein angiography that the delay in choroidal filling is followed by late leakage from choroidal vessels into the subretinal space. The leakage is enhanced by infarction and damage to the RPE cells or transudation of fluid into the subretinal space in response to increased pressure in the choroidal vessels.  Focal occlusion of the choriocapillaris leads to necrosis and atrophy of the RPE, forming Elschnig’s spots ( Fig. 113-5 ).  Acutely, Elschnig’s spots are punctate, tan-white lesions that leak on fluorescein and indocyanine green angiography from breakdown in the blood-retina barrier. Subretinal fluid accumulates, with the eventual formation of macular edema, a common finding associated with hypertensive choroidopathy ( Fig. 113-6 ). With time, the focal RPE lesions become confluent and more extensive. Diffuse pigmentary changes with atrophy give a mottled appearance on ophthalmoscopy. Linear configurations of pigmentation along choroidal arteries are known as Siegrist’s streaks.
Hypertensive optic neuropathy presents clinically as disc edema ( Fig. 113-7 ). This occurs from vasoconstriction of the posterior ciliary arteries supplying the optic nerve head, resulting from the release of angiotensin II and other vasoconstricting agents. Ischemia occurs in the optic nerve, leading to stasis of axoplasmic flow, which is a form of anterior ischemic optic neuropathy. For the differential diagnosis, see Box 113-2 .
Figure 113-5 Elschnig’s spots.
Figure 113-6 Serous detachment of the retina in a 27-year-old patient who has pregnancy-induced hypertension, 3 days postpartum. Blood pressure measured 158/100?mmHg. Note the subretinal fibrin and folds in the retina. (Courtesy of Franklin L Myers.)
Figure 113-7 Bilateral optic nerve edema. Associated subretinal fluid, flame-shaped hemorrhages, and lipid exudation in a macular star configuration are evident in this patient with malignant hypertensive retinopathy.
Differential Diagnosis of Acute Hypertensive Retinopathy
Bilateral bullous central serous chorioretinopathy
Bilateral central retinal vein obstruction
Collagen vascular diseases
Diabetic retinopathy (especially in the setting of diabetic papillopathy)
DIAGNOSIS AND ANCILLARY TESTING
Hypertensive retinopathy is a clinical diagnosis made when the characteristic fundus findings are visualized on slit-lamp biomicroscopy in a patient with systemic arterial hypertension. Fluorescein angiography may be used, but it is not crucial in the diagnosis. Angiographic findings as described earlier are more common in malignant hypertension. Measurement of systemic blood pressure is necessary to rule out other causes with similar clinical pictures.
Several classification schemes have been used to stage hypertensive retinal changes. The two most widely accepted are the Keith-Wagener-Barker classification and the Scheie classification. The Keith-Wagener-Barker scheme ( Table 113-1 ) combines the clinical findings of hypertension and atherosclerosis.  The Scheie classification ( Table 113-2 ) keeps the two disease processes separate. Unfortunately, no classification is satisfactory because of the high variability of clinical findings. They are of historical value only and are not used clinically; accurate description of the ocular findings is more valuable than any classification system.
Although newer imaging techniques, such as scanning laser ophthalmoscopy, allow quantification of retinal capillary density
TABLE 113-1 — KEITH-WAGENER-BARKER CLASSIFICATION
Mild-to-moderate narrowing or sclerosis of the arterioles
Moderate to marked narrowing of the arterioles
Local and/or generalized narrowing of arterioles
Exaggeration of the light reflex
Arteriovenous crossing changes
Retinal arteriolar narrowing and focal constriction
As for Group 3, plus papilledema
(Adapted from Walsh JB. Hypertensive retinopathy. Description, classification and prognosis. Ophthalmology. 1981;89:1127–31.)
TABLE 113-2 — SCHEIE CLASSIFICATION
Barely detectable arteriolar narrowing
Obvious arteriolar narrowing with focal irregularities
Grade 2 plus retinal hemorrhages and/or exudates
Grade 3 plus papilledema
Barely detectable light reflex changes
Obvious increased light reflex changes
and flow velocity in patients who have essential hypertension, these results are still preliminary in terms of their application to the long-term prevention of retinal disease. Optical coherence tomography may be used to evaluate cross-sectional images of the retina and subretinal fluid collections.
Essential hypertension is the most common cause of chronically elevated blood pressure and is typically of unknown cause. Screening for secondary systemic causes is not pursued unless other symptoms are present or the hypertension is resistant to treatment. The causes of secondary hypertension include pheochromocytoma, renovascular stenosis, and primary hyperaldosteronism. 
In nearly all cases of malignant hypertension, a systemic cause can be elucidated via systemic evaluation. Potential causes include renal disease, such as polycystic kidney or renovascular stenosis; pheochromocytoma; and pregnancy. Rarely, untreated essential hypertension may lead to an acute hypertensive crisis. Systemic abnormalities accompany accelerated hypertension with evidence of end-organ damage, including acute left ventricular heart failure, myocardial infarction, pulmonary edema, dissecting aortic aneurysm, stroke, encephalopathy, and intracranial hemorrhage.  
Microscopically, early changes from hypertension demonstrate sclerosis and thickening of the arteriolar walls with luminal narrowing. These findings become more prominent with long-standing systemic hypertension. Arteriole thickening in the choroidal vessels is typically more severe than in the retinal arterioles
and more closely resembles systemic arterial changes. In malignant hypertension, the arterioles are similarly thickened, but necrosis and fibrinoid deposition in the vessel wall occur. Electron micrographs of retinal arterioles in malignant hypertension eventually demonstrate dilatation of the lumen, with focal breaks in the endothelium surrounded by lipid and fibrin, as the autoregulatory mechanisms of the arterioles are exceeded.  Other pathological findings include optic nerve edema, cotton-wool spots, microaneurysms, and focal infarcts.
TREATMENT, COURSE, AND OUTCOME
By itself, chronic hypertensive retinopathy rarely, if ever, results in significant loss of vision. Treatment of the underlying systemic condition can halt the progress of the retinal changes, but arteriolar narrowing and arteriovenous nicking usually are permanent.
Treatment of malignant hypertensive retinopathy, choroidopathy, and optic neuropathy consists of lowering blood pressure in a controlled fashion to a level that minimizes end-organ damage. The actual level of blood pressure is less important in gauging the urgency of the situation than is the ongoing end-organ damage. In hypertensive patients, the autoregulatory mechanism that maintains constant blood flow to tissues is elevated to a higher level. This allows for the tolerance of higher blood pressures, and lowering blood pressure below the regulatory range can prevent adequate blood flow from reaching vital organs. Therefore, blood pressure should be lowered in a slow, deliberate, controlled fashion to prevent end-organ damage. Too rapid a decline can lead to ischemia of the optic nerve head, brain, and other vital organs, resulting in permanent damage. Medications used to treat hypertensive emergencies include sodium nitroprusside, nitroglycerin, calcium channel blockers, ß-blockers, and angiotensin-converting enzyme inhibitors. Treatment should be initiated in a controlled, monitored setting under the auspices of a physician skilled in the use of antihypertensive medications.
From a systemic viewpoint, the diagnosis of a malignant hypertensive crisis represents a medical emergency. Untreated, the mortality rate is 50% at 2 months and 90% at 1 year.  Most patients resume normal vision. On the rare occasion when vision loss occurs, this may result from retinal pigment changes secondary to retinal detachment or from optic atrophy due to prolonged papilledema.
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